HUP0303436A2 - Diaril-peptidek mint a hepatitis C vírus NS3-szerin proteáz inhibitorai, ezeket tartalmazó gyógyszerkészítmények és alkalmazásuk - Google Patents

Diaril-peptidek mint a hepatitis C vírus NS3-szerin proteáz inhibitorai, ezeket tartalmazó gyógyszerkészítmények és alkalmazásuk Download PDF

Info

Publication number: HUP0303436A2
Authority: HU; Hungary
Prior art keywords: group; alkyl; compounds according; aryl; hydrogen
Prior art date: 2000-12-12

Application number

HU0303436A

Other languages

English (en)

Hungarian (hu)

Inventor

Ashok Arasappan

Kevin X. Chen

Viyyoor M. Girijavallabhan

Raymond G. Lovey

Bruce A. Malcolm

F. George Njoroge

Zhong-Yue Sun

Srikanth Venkatraman

Zhaoning Zhu

Original Assignee

Schering Corp.

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2000-12-12

Filing date

2001-12-10

Publication date

2004-01-28

2001-12-10 Application filed by Schering Corp. filed Critical Schering Corp.

2004-01-28 Publication of HUP0303436A2 publication Critical patent/HUP0303436A2/hu

Links

239000008194 pharmaceutical composition Substances 0.000 title claims description 39
241000711549 Hepacivirus C Species 0.000 title description 36
108090000765 processed proteins & peptides Proteins 0.000 title description 17
102000004196 processed proteins & peptides Human genes 0.000 title description 14
YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 title description 4
239000003001 serine protease inhibitor Substances 0.000 title description 4
150000001875 compounds Chemical class 0.000 claims abstract description 213
-1 methylene- Chemical class 0.000 claims abstract description 143
125000000217 alkyl group Chemical group 0.000 claims abstract description 106
125000003342 alkenyl group Chemical group 0.000 claims abstract description 52
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 50
125000003118 aryl group Chemical group 0.000 claims abstract description 48
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 48
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 44
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 43
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 42
238000000034 method Methods 0.000 claims abstract description 40
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 39
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 35
229910052717 sulfur Inorganic materials 0.000 claims abstract description 33
229910052760 oxygen Inorganic materials 0.000 claims abstract description 32
239000001301 oxygen Substances 0.000 claims abstract description 32
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 31
125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 29
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 25
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 25
125000000304 alkynyl group Chemical group 0.000 claims abstract description 23
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 22
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims abstract description 22
125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 22
239000011593 sulfur Substances 0.000 claims abstract description 22
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims abstract description 19
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims abstract description 14
125000004434 sulfur atom Chemical group 0.000 claims abstract description 13
125000004429 atom Chemical group 0.000 claims abstract description 7
125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 7
125000004404 heteroalkyl group Chemical group 0.000 claims abstract description 5
238000004519 manufacturing process Methods 0.000 claims abstract description 4
125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims abstract description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 98
239000000203 mixture Substances 0.000 claims description 79
239000001257 hydrogen Substances 0.000 claims description 52
229910052739 hydrogen Inorganic materials 0.000 claims description 52
125000004432 carbon atom Chemical group C* 0.000 claims description 50
150000002431 hydrogen Chemical class 0.000 claims description 38
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 33
125000003545 alkoxy group Chemical group 0.000 claims description 32
125000001424 substituent group Chemical group 0.000 claims description 29
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 28
125000002877 alkyl aryl group Chemical group 0.000 claims description 28
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 23
125000000623 heterocyclic group Chemical group 0.000 claims description 23
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
239000004480 active ingredient Substances 0.000 claims description 22
125000003282 alkyl amino group Chemical group 0.000 claims description 22
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 22
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
125000001841 imino group Chemical group [H]N=* 0.000 claims description 21
125000004414 alkyl thio group Chemical group 0.000 claims description 20
125000005110 aryl thio group Chemical group 0.000 claims description 20
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 20
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 19
125000004104 aryloxy group Chemical group 0.000 claims description 18
125000005343 heterocyclic alkyl group Chemical group 0.000 claims description 18
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 18
201000010099 disease Diseases 0.000 claims description 17
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
125000001769 aryl amino group Chemical group 0.000 claims description 16
108091005804 Peptidases Proteins 0.000 claims description 15
239000004365 Protease Substances 0.000 claims description 15
238000002360 preparation method Methods 0.000 claims description 15
125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 14
125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 14
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 14
125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 14
125000005281 alkyl ureido group Chemical group 0.000 claims description 14
125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 14
125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 14
125000005421 aryl sulfonamido group Chemical group 0.000 claims description 14
125000004446 heteroarylalkyl group Chemical group 0.000 claims description 14
125000004437 phosphorous atom Chemical group 0.000 claims description 14
229910052698 phosphorus Inorganic materials 0.000 claims description 13
150000003839 salts Chemical class 0.000 claims description 13
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 12
125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 11
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 11
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 11
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 10
125000006325 2-propenyl amino group Chemical group [H]C([H])=C([H])C([H])([H])N([H])* 0.000 claims description 10
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 10
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 10
229910052786 argon Inorganic materials 0.000 claims description 10
125000005129 aryl carbonyl group Chemical group 0.000 claims description 10
230000000694 effects Effects 0.000 claims description 10
229910052736 halogen Inorganic materials 0.000 claims description 9
150000002367 halogens Chemical class 0.000 claims description 9
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 9
239000012453 solvate Substances 0.000 claims description 9
102000014150 Interferons Human genes 0.000 claims description 8
108010050904 Interferons Proteins 0.000 claims description 8
241000700605 Viruses Species 0.000 claims description 8
125000005518 carboxamido group Chemical group 0.000 claims description 8
239000003937 drug carrier Substances 0.000 claims description 8
125000005226 heteroaryloxycarbonyl group Chemical group 0.000 claims description 8
125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 8
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 8
229940079322 interferon Drugs 0.000 claims description 8
125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 8
125000005843 halogen group Chemical group 0.000 claims description 7
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 claims description 6
150000001204 N-oxides Chemical class 0.000 claims description 6
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 6
125000005135 aryl sulfinyl group Chemical group 0.000 claims description 6
125000005708 carbonyloxy group Chemical group [*:2]OC([*:1])=O 0.000 claims description 6
125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims description 6
125000005150 heteroarylsulfinyl group Chemical group 0.000 claims description 6
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
125000003003 spiro group Chemical group 0.000 claims description 6
125000003396 thiol group Chemical class [H]S* 0.000 claims description 6
125000004665 trialkylsilyl group Chemical group 0.000 claims description 6
125000003275 alpha amino acid group Chemical group 0.000 claims description 5
229910052799 carbon Inorganic materials 0.000 claims description 5
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
208000015181 infectious disease Diseases 0.000 claims description 5
230000002401 inhibitory effect Effects 0.000 claims description 5
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 4
230000000840 anti-viral effect Effects 0.000 claims description 4
125000005002 aryl methyl group Chemical group 0.000 claims description 4
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 4
239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 4
229960000329 ribavirin Drugs 0.000 claims description 4
HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims description 4
230000001747 exhibiting effect Effects 0.000 claims description 3
PZIDJKOIMRBQLL-UHFFFAOYSA-N $l^{2}-azanylidenemethane Chemical compound [N]=C PZIDJKOIMRBQLL-UHFFFAOYSA-N 0.000 claims description 2
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
DBTDEFJAFBUGPP-UHFFFAOYSA-N Methanethial Chemical compound S=C DBTDEFJAFBUGPP-UHFFFAOYSA-N 0.000 claims description 2
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 2
125000004947 alkyl aryl amino group Chemical group 0.000 claims description 2
150000001346 alkyl aryl ethers Chemical class 0.000 claims description 2
150000004789 alkyl aryl sulfoxides Chemical class 0.000 claims description 2
125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 2
150000005215 alkyl ethers Chemical class 0.000 claims description 2
125000004422 alkyl sulphonamide group Chemical group 0.000 claims description 2
125000003368 amide group Chemical group 0.000 claims description 2
125000005199 aryl carbonyloxy group Chemical group 0.000 claims description 2
150000008378 aryl ethers Chemical class 0.000 claims description 2
125000005362 aryl sulfone group Chemical group 0.000 claims description 2
125000004421 aryl sulphonamide group Chemical group 0.000 claims description 2
150000001721 carbon Chemical group 0.000 claims description 2
125000006165 cyclic alkyl group Chemical group 0.000 claims description 2
125000004122 cyclic group Chemical group 0.000 claims description 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
239000003814 drug Substances 0.000 claims description 2
239000011737 fluorine Substances 0.000 claims description 2
229910052731 fluorine Inorganic materials 0.000 claims description 2
125000005222 heteroarylaminocarbonyl group Chemical group 0.000 claims description 2
125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 2
125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 2
239000011574 phosphorus Substances 0.000 claims description 2
125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 2
102000006992 Interferon-alpha Human genes 0.000 claims 3
108010047761 Interferon-alpha Proteins 0.000 claims 3
102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims 3
239000003443 antiviral agent Substances 0.000 claims 3
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims 2
125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 1
125000006374 C2-C10 alkenyl group Chemical group 0.000 claims 1
229940124158 Protease/peptidase inhibitor Drugs 0.000 claims 1
208000005176 Hepatitis C Diseases 0.000 abstract description 10
230000008569 process Effects 0.000 abstract description 5
125000000547 substituted alkyl group Chemical group 0.000 abstract 3
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 abstract 1
AFCIMSXHQSIHQW-UHFFFAOYSA-N [O].[P] Chemical compound [O].[P] AFCIMSXHQSIHQW-UHFFFAOYSA-N 0.000 abstract 1
XOCUXOWLYLLJLV-UHFFFAOYSA-N [O].[S] Chemical group [O].[S] XOCUXOWLYLLJLV-UHFFFAOYSA-N 0.000 abstract 1
239000000825 pharmaceutical preparation Substances 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 134
239000000243 solution Substances 0.000 description 108
239000000047 product Substances 0.000 description 50
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 47
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 46
235000019439 ethyl acetate Nutrition 0.000 description 44
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 42
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 34
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 31
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
239000011541 reaction mixture Substances 0.000 description 26
238000006243 chemical reaction Methods 0.000 description 25
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 25
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 21
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
239000007787 solid Substances 0.000 description 19
239000000758 substrate Substances 0.000 description 18
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
239000000706 filtrate Substances 0.000 description 16
235000011007 phosphoric acid Nutrition 0.000 description 16
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 15
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
229910000147 aluminium phosphate Inorganic materials 0.000 description 15
239000003112 inhibitor Substances 0.000 description 15
235000002639 sodium chloride Nutrition 0.000 description 15
101710144111 Non-structural protein 3 Proteins 0.000 description 13
239000010410 layer Substances 0.000 description 13
239000000843 powder Substances 0.000 description 13
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
102000035195 Peptidases Human genes 0.000 description 12
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
238000000746 purification Methods 0.000 description 12
239000000741 silica gel Substances 0.000 description 12
229910002027 silica gel Inorganic materials 0.000 description 12
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 12
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 11
108010022999 Serine Proteases Proteins 0.000 description 11
102000012479 Serine Proteases Human genes 0.000 description 11
229910000402 monopotassium phosphate Inorganic materials 0.000 description 11
235000019796 monopotassium phosphate Nutrition 0.000 description 11
PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 11
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 10
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 10
238000005859 coupling reaction Methods 0.000 description 10
239000002552 dosage form Substances 0.000 description 10
239000000284 extract Substances 0.000 description 10
239000000314 lubricant Substances 0.000 description 10
238000003756 stirring Methods 0.000 description 10
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
235000001014 amino acid Nutrition 0.000 description 9
239000000463 material Substances 0.000 description 9
239000012044 organic layer Substances 0.000 description 9
239000003826 tablet Substances 0.000 description 9
229920002472 Starch Polymers 0.000 description 8
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
238000003556 assay Methods 0.000 description 8
239000003085 diluting agent Substances 0.000 description 8
235000019441 ethanol Nutrition 0.000 description 8
239000011780 sodium chloride Substances 0.000 description 8
235000019698 starch Nutrition 0.000 description 8
150000001413 amino acids Chemical class 0.000 description 7
239000011230 binding agent Substances 0.000 description 7
238000003776 cleavage reaction Methods 0.000 description 7
230000008878 coupling Effects 0.000 description 7
238000010168 coupling process Methods 0.000 description 7
229910052943 magnesium sulfate Inorganic materials 0.000 description 7
235000019341 magnesium sulphate Nutrition 0.000 description 7
235000018102 proteins Nutrition 0.000 description 7
108090000623 proteins and genes Proteins 0.000 description 7
102000004169 proteins and genes Human genes 0.000 description 7
230000007017 scission Effects 0.000 description 7
239000002904 solvent Substances 0.000 description 7
239000000725 suspension Substances 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
238000005481 NMR spectroscopy Methods 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
239000002253 acid Substances 0.000 description 6
239000002775 capsule Substances 0.000 description 6
239000003153 chemical reaction reagent Substances 0.000 description 6
239000007884 disintegrant Substances 0.000 description 6
239000008187 granular material Substances 0.000 description 6
238000001819 mass spectrum Methods 0.000 description 6
229920006395 saturated elastomer Polymers 0.000 description 6
239000000126 substance Substances 0.000 description 6
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 6
238000004809 thin layer chromatography Methods 0.000 description 6
HJBLUNHMOKFZQX-UHFFFAOYSA-N 3-hydroxy-1,2,3-benzotriazin-4-one Chemical compound C1=CC=C2C(=O)N(O)N=NC2=C1 HJBLUNHMOKFZQX-UHFFFAOYSA-N 0.000 description 5
102000004190 Enzymes Human genes 0.000 description 5
108090000790 Enzymes Proteins 0.000 description 5
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 5
239000012131 assay buffer Substances 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
229940088598 enzyme Drugs 0.000 description 5
150000002148 esters Chemical class 0.000 description 5
239000007788 liquid Substances 0.000 description 5
229920001184 polypeptide Polymers 0.000 description 5
238000012545 processing Methods 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
239000008107 starch Substances 0.000 description 5
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
108010010803 Gelatin Proteins 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
229910052796 boron Inorganic materials 0.000 description 4
239000004202 carbamide Substances 0.000 description 4
238000007906 compression Methods 0.000 description 4
230000006835 compression Effects 0.000 description 4
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 4
229960001760 dimethyl sulfoxide Drugs 0.000 description 4
239000000839 emulsion Substances 0.000 description 4
238000003818 flash chromatography Methods 0.000 description 4
229920000159 gelatin Polymers 0.000 description 4
235000019322 gelatine Nutrition 0.000 description 4
235000011852 gelatine desserts Nutrition 0.000 description 4
239000000543 intermediate Substances 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
229920000609 methyl cellulose Polymers 0.000 description 4
239000001923 methylcellulose Substances 0.000 description 4
235000010981 methylcellulose Nutrition 0.000 description 4
230000003647 oxidation Effects 0.000 description 4
238000007254 oxidation reaction Methods 0.000 description 4
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 4
JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 4
239000007921 spray Substances 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
239000001993 wax Substances 0.000 description 4
125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 3
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 3
238000005160 1H NMR spectroscopy Methods 0.000 description 3
FVMDYYGIDFPZAX-UHFFFAOYSA-N 3-hydroxyphenylacetic acid Chemical compound OC(=O)CC1=CC=CC(O)=C1 FVMDYYGIDFPZAX-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
229920000168 Microcrystalline cellulose Polymers 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
229930006000 Sucrose Natural products 0.000 description 3
240000008042 Zea mays Species 0.000 description 3
235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 3
235000002017 Zea mays subsp mays Nutrition 0.000 description 3
235000010443 alginic acid Nutrition 0.000 description 3
229920000615 alginic acid Polymers 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
239000001768 carboxy methyl cellulose Substances 0.000 description 3
239000000969 carrier Substances 0.000 description 3
235000010980 cellulose Nutrition 0.000 description 3
229920002678 cellulose Polymers 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
239000003086 colorant Substances 0.000 description 3
238000001816 cooling Methods 0.000 description 3
235000005822 corn Nutrition 0.000 description 3
239000012043 crude product Substances 0.000 description 3
229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 3
NLEBIOOXCVAHBD-QKMCSOCLSA-N dodecyl beta-D-maltoside Chemical compound O[C@@H]1[C@@H](O)[C@H](OCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 NLEBIOOXCVAHBD-QKMCSOCLSA-N 0.000 description 3
235000003599 food sweetener Nutrition 0.000 description 3
239000008273 gelatin Substances 0.000 description 3
206010073071 hepatocellular carcinoma Diseases 0.000 description 3
231100000844 hepatocellular carcinoma Toxicity 0.000 description 3
238000012417 linear regression Methods 0.000 description 3
235000019813 microcrystalline cellulose Nutrition 0.000 description 3
230000004048 modification Effects 0.000 description 3
238000012986 modification Methods 0.000 description 3
239000003921 oil Substances 0.000 description 3
230000003287 optical effect Effects 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
235000010413 sodium alginate Nutrition 0.000 description 3
239000000661 sodium alginate Substances 0.000 description 3
229940005550 sodium alginate Drugs 0.000 description 3
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
229910052938 sodium sulfate Inorganic materials 0.000 description 3
235000011152 sodium sulphate Nutrition 0.000 description 3
239000005720 sucrose Substances 0.000 description 3
235000000346 sugar Nutrition 0.000 description 3
150000008163 sugars Chemical class 0.000 description 3
230000004083 survival effect Effects 0.000 description 3
239000003765 sweetening agent Substances 0.000 description 3
208000024891 symptom Diseases 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Substances C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 3
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
HSHNITRMYYLLCV-UHFFFAOYSA-N 4-methylumbelliferone Chemical compound C1=C(O)C=CC2=C1OC(=O)C=C2C HSHNITRMYYLLCV-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
241000416162 Astragalus gummifer Species 0.000 description 2
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
241000701022 Cytomegalovirus Species 0.000 description 2
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
229920002907 Guar gum Polymers 0.000 description 2
239000007821 HATU Substances 0.000 description 2
229940124771 HCV-NS3 protease inhibitor Drugs 0.000 description 2
241000709721 Hepatovirus A Species 0.000 description 2
241000701044 Human gammaherpesvirus 4 Species 0.000 description 2
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
240000007472 Leucaena leucocephala Species 0.000 description 2
235000010643 Leucaena leucocephala Nutrition 0.000 description 2
239000007993 MOPS buffer Substances 0.000 description 2
229930195725 Mannitol Natural products 0.000 description 2
101800001020 Non-structural protein 4A Proteins 0.000 description 2
240000007594 Oryza sativa Species 0.000 description 2
235000007164 Oryza sativa Nutrition 0.000 description 2
108010033276 Peptide Fragments Proteins 0.000 description 2
102000007079 Peptide Fragments Human genes 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
101800001838 Serine protease/helicase NS3 Proteins 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
229920001615 Tragacanth Polymers 0.000 description 2
RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 2
241000209140 Triticum Species 0.000 description 2
235000021307 Triticum Nutrition 0.000 description 2
238000002835 absorbance Methods 0.000 description 2
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
239000000443 aerosol Substances 0.000 description 2
239000000783 alginic acid Substances 0.000 description 2
229960001126 alginic acid Drugs 0.000 description 2
150000004781 alginic acids Chemical class 0.000 description 2
210000004899 c-terminal region Anatomy 0.000 description 2
CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical class [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 2
OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
239000001913 cellulose Substances 0.000 description 2
208000019425 cirrhosis of liver Diseases 0.000 description 2
238000004040 coloring Methods 0.000 description 2
238000013270 controlled release Methods 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 2
238000001035 drying Methods 0.000 description 2
239000003480 eluent Substances 0.000 description 2
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 2
238000001914 filtration Methods 0.000 description 2
239000000499 gel Substances 0.000 description 2
239000011521 glass Substances 0.000 description 2
235000010417 guar gum Nutrition 0.000 description 2
239000000665 guar gum Substances 0.000 description 2
229960002154 guar gum Drugs 0.000 description 2
208000006454 hepatitis Diseases 0.000 description 2
231100000283 hepatitis Toxicity 0.000 description 2
208000010710 hepatitis C virus infection Diseases 0.000 description 2
208000029570 hepatitis D virus infection Diseases 0.000 description 2
238000004128 high performance liquid chromatography Methods 0.000 description 2
239000008101 lactose Substances 0.000 description 2
208000019423 liver disease Diseases 0.000 description 2
235000019359 magnesium stearate Nutrition 0.000 description 2
239000000594 mannitol Substances 0.000 description 2
235000010355 mannitol Nutrition 0.000 description 2
239000011159 matrix material Substances 0.000 description 2
238000002844 melting Methods 0.000 description 2
229940098779 methanesulfonic acid Drugs 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 2
150000004702 methyl esters Chemical class 0.000 description 2
GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 2
229940016286 microcrystalline cellulose Drugs 0.000 description 2
239000008108 microcrystalline cellulose Substances 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
230000001590 oxidative effect Effects 0.000 description 2
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
229920001223 polyethylene glycol Polymers 0.000 description 2
229920000642 polymer Polymers 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
239000003755 preservative agent Substances 0.000 description 2
239000011347 resin Substances 0.000 description 2
229920005989 resin Polymers 0.000 description 2
235000009566 rice Nutrition 0.000 description 2
YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
238000000926 separation method Methods 0.000 description 2
239000000377 silicon dioxide Substances 0.000 description 2
239000001632 sodium acetate Substances 0.000 description 2
235000017281 sodium acetate Nutrition 0.000 description 2
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 2
239000004299 sodium benzoate Substances 0.000 description 2
235000010234 sodium benzoate Nutrition 0.000 description 2
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 2
238000001228 spectrum Methods 0.000 description 2
239000007858 starting material Substances 0.000 description 2
238000006467 substitution reaction Methods 0.000 description 2
239000000829 suppository Substances 0.000 description 2
239000012730 sustained-release form Substances 0.000 description 2
239000000454 talc Substances 0.000 description 2
229910052623 talc Inorganic materials 0.000 description 2
235000012222 talc Nutrition 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
235000010487 tragacanth Nutrition 0.000 description 2
239000000196 tragacanth Substances 0.000 description 2
229940116362 tragacanth Drugs 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 2
239000003039 volatile agent Substances 0.000 description 2
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
JBIJSEUVWWLFGV-SFHVURJKSA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)pentanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](CCC)C(O)=O)C3=CC=CC=C3C2=C1 JBIJSEUVWWLFGV-SFHVURJKSA-N 0.000 description 1
QSUXZIPXYDQFCX-JTQLQIEISA-N (2s)-2-cyclohexyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)C1CCCCC1 QSUXZIPXYDQFCX-JTQLQIEISA-N 0.000 description 1
BENKAPCDIOILGV-RQJHMYQMSA-N (2s,4r)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1C[C@H](O)C[C@H]1C(O)=O BENKAPCDIOILGV-RQJHMYQMSA-N 0.000 description 1
JXDNUMOTWHZSCB-XMTZKCFKSA-N (3s)-3-acetamido-4-[[(2s)-3-carboxy-1-[[(2s,3s)-1-[[(2s)-1-[(2s)-2-[[(1r)-1-carboxy-2-sulfanylethyl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid Chemical compound OC(=O)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CS)C(O)=O JXDNUMOTWHZSCB-XMTZKCFKSA-N 0.000 description 1
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
RNHDAKUGFHSZEV-UHFFFAOYSA-N 1,4-dioxane;hydrate Chemical compound O.C1COCCO1 RNHDAKUGFHSZEV-UHFFFAOYSA-N 0.000 description 1
VVKAGQHUUDRPOI-NEPJUHHUSA-N 1-o-benzyl 2-o-methyl (2s,4r)-4-hydroxypyrrolidine-1,2-dicarboxylate Chemical compound COC(=O)[C@@H]1C[C@@H](O)CN1C(=O)OCC1=CC=CC=C1 VVKAGQHUUDRPOI-NEPJUHHUSA-N 0.000 description 1
NLBWWURQVQBCBC-UHFFFAOYSA-N 2-[[2-[(1-carboxy-3-methylbutyl)amino]-2-oxoacetyl]amino]-4-methylpentanoic acid Chemical compound CC(C)CC(C(O)=O)NC(=O)C(=O)NC(C(O)=O)CC(C)C NLBWWURQVQBCBC-UHFFFAOYSA-N 0.000 description 1
IDWHSUSIOBKSKI-UHFFFAOYSA-N 2-[cyclohexyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]acetic acid Chemical compound CC(C)(C)OC(=O)N(CC(O)=O)C1CCCCC1 IDWHSUSIOBKSKI-UHFFFAOYSA-N 0.000 description 1
LRFZIPCTFBPFLX-UHFFFAOYSA-N 3,3-dimethyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical compound CC(C)(C)OC(=O)NC(C(O)=O)C(C)(C)C LRFZIPCTFBPFLX-UHFFFAOYSA-N 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
BEYOBVMPDRKTNR-BUHFOSPRSA-N 4-Hydroxyazobenzene Chemical compound C1=CC(O)=CC=C1\N=N\C1=CC=CC=C1 BEYOBVMPDRKTNR-BUHFOSPRSA-N 0.000 description 1
KMMHZIBWCXYAAH-UHFFFAOYSA-N 4-bromobenzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=C(Br)C=C1 KMMHZIBWCXYAAH-UHFFFAOYSA-N 0.000 description 1
229960000549 4-dimethylaminophenol Drugs 0.000 description 1
BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 1
WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 1
229920001817 Agar Polymers 0.000 description 1
208000022309 Alcoholic Liver disease Diseases 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
229910015900 BF3 Inorganic materials 0.000 description 1
208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 1
208000033222 Biliary cirrhosis primary Diseases 0.000 description 1
101710132601 Capsid protein Proteins 0.000 description 1
229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
102000053642 Catalytic RNA Human genes 0.000 description 1
108090000994 Catalytic RNA Proteins 0.000 description 1
108090000317 Chymotrypsin Proteins 0.000 description 1
101710094648 Coat protein Proteins 0.000 description 1
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
235000019739 Dicalciumphosphate Nutrition 0.000 description 1
241000196324 Embryophyta Species 0.000 description 1
OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
244000166102 Eucalyptus leucoxylon Species 0.000 description 1
235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 1
108010074860 Factor Xa Proteins 0.000 description 1
108010088842 Fibrinolysin Proteins 0.000 description 1
206010016654 Fibrosis Diseases 0.000 description 1
241000206672 Gelidium Species 0.000 description 1
102100021181 Golgi phosphoprotein 3 Human genes 0.000 description 1
229940122604 HCV protease inhibitor Drugs 0.000 description 1
241000700721 Hepatitis B virus Species 0.000 description 1
208000005331 Hepatitis D Diseases 0.000 description 1
101000856199 Homo sapiens Chymotrypsin-like protease CTRL-1 Proteins 0.000 description 1
102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
125000003440 L-leucyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C(C([H])([H])[H])([H])C([H])([H])[H] 0.000 description 1
102000006835 Lamins Human genes 0.000 description 1
108010047294 Lamins Proteins 0.000 description 1
229920000161 Locust bean gum Polymers 0.000 description 1
101710125418 Major capsid protein Proteins 0.000 description 1
229920000881 Modified starch Polymers 0.000 description 1
101100129514 Mus musculus Mbip gene Proteins 0.000 description 1
125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
229910019093 NaOCl Inorganic materials 0.000 description 1
108090001074 Nucleocapsid Proteins Proteins 0.000 description 1
101710141454 Nucleoprotein Proteins 0.000 description 1
241001165050 Ocala Species 0.000 description 1
108010067372 Pancreatic elastase Proteins 0.000 description 1
102000016387 Pancreatic elastase Human genes 0.000 description 1
101710126321 Pancreatic trypsin inhibitor Proteins 0.000 description 1
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
108010076039 Polyproteins Proteins 0.000 description 1
239000004372 Polyvinyl alcohol Substances 0.000 description 1
208000012654 Primary biliary cholangitis Diseases 0.000 description 1
101710083689 Probable capsid protein Proteins 0.000 description 1
108010049219 RNA-dependent ATPase Proteins 0.000 description 1
229940122055 Serine protease inhibitor Drugs 0.000 description 1
101710102218 Serine protease inhibitor Proteins 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
239000004902 Softening Agent Substances 0.000 description 1
244000061456 Solanum tuberosum Species 0.000 description 1
235000002595 Solanum tuberosum Nutrition 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
240000001058 Sterculia urens Species 0.000 description 1
235000015125 Sterculia urens Nutrition 0.000 description 1
101710172711 Structural protein Proteins 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
239000004473 Threonine Substances 0.000 description 1
108090000190 Thrombin Proteins 0.000 description 1
108090000631 Trypsin Proteins 0.000 description 1
102000004142 Trypsin Human genes 0.000 description 1
108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
239000003463 adsorbent Substances 0.000 description 1
235000010419 agar Nutrition 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
125000000539 amino acid group Chemical group 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
239000000908 ammonium hydroxide Substances 0.000 description 1
239000000538 analytical sample Substances 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
235000006708 antioxidants Nutrition 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
150000001540 azides Chemical class 0.000 description 1
235000012216 bentonite Nutrition 0.000 description 1
125000002619 bicyclic group Chemical group 0.000 description 1
230000008033 biological extinction Effects 0.000 description 1
210000000988 bone and bone Anatomy 0.000 description 1
KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
239000004327 boric acid Substances 0.000 description 1
235000010338 boric acid Nutrition 0.000 description 1
239000000872 buffer Substances 0.000 description 1
239000004067 bulking agent Substances 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
235000010410 calcium alginate Nutrition 0.000 description 1
239000000648 calcium alginate Substances 0.000 description 1
229960002681 calcium alginate Drugs 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
235000013539 calcium stearate Nutrition 0.000 description 1
239000008116 calcium stearate Substances 0.000 description 1
235000011132 calcium sulphate Nutrition 0.000 description 1
DIOLOCSXUMYFJN-UHFFFAOYSA-N calcium;azane Chemical compound N.[Ca+2] DIOLOCSXUMYFJN-UHFFFAOYSA-N 0.000 description 1
235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
239000008112 carboxymethyl-cellulose Substances 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
238000006555 catalytic reaction Methods 0.000 description 1
230000008859 change Effects 0.000 description 1
238000012512 characterization method Methods 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
229960002376 chymotrypsin Drugs 0.000 description 1
239000003541 chymotrypsin inhibitor Substances 0.000 description 1
230000007882 cirrhosis Effects 0.000 description 1
239000004927 clay Substances 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
230000000052 comparative effect Effects 0.000 description 1
230000002860 competitive effect Effects 0.000 description 1
230000006957 competitive inhibition Effects 0.000 description 1
239000013068 control sample Substances 0.000 description 1
239000006071 cream Substances 0.000 description 1
235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
235000018417 cysteine Nutrition 0.000 description 1
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
230000006378 damage Effects 0.000 description 1
239000007933 dermal patch Substances 0.000 description 1
238000013461 design Methods 0.000 description 1
NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 1
238000003745 diagnosis Methods 0.000 description 1
NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
229940038472 dicalcium phosphate Drugs 0.000 description 1
229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
MGHPNCMVUAKAIE-UHFFFAOYSA-N diphenylmethanamine Chemical compound C=1C=CC=CC=1C(N)C1=CC=CC=C1 MGHPNCMVUAKAIE-UHFFFAOYSA-N 0.000 description 1
238000007907 direct compression Methods 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
229940079593 drug Drugs 0.000 description 1
238000007908 dry granulation Methods 0.000 description 1
241001493065 dsRNA viruses Species 0.000 description 1
239000000975 dye Substances 0.000 description 1
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
239000003974 emollient agent Substances 0.000 description 1
238000010931 ester hydrolysis Methods 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000002979 fabric softener Substances 0.000 description 1
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
235000013305 food Nutrition 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
238000009472 formulation Methods 0.000 description 1
235000015203 fruit juice Nutrition 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
229960002598 fumaric acid Drugs 0.000 description 1
235000011087 fumaric acid Nutrition 0.000 description 1
CRLNTRZMHKNJSR-UHFFFAOYSA-N furan-2-yl(phenyl)methanone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CO1 CRLNTRZMHKNJSR-UHFFFAOYSA-N 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000003292 glue Substances 0.000 description 1
239000007902 hard capsule Substances 0.000 description 1
108700012707 hepatitis C virus NS3 Proteins 0.000 description 1
239000000833 heterodimer Substances 0.000 description 1
238000013537 high throughput screening Methods 0.000 description 1
239000008240 homogeneous mixture Substances 0.000 description 1
235000012907 honey Nutrition 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
230000036039 immunity Effects 0.000 description 1
230000000937 inactivator Effects 0.000 description 1
230000006698 induction Effects 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
229910010272 inorganic material Inorganic materials 0.000 description 1
239000011147 inorganic material Substances 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
230000003993 interaction Effects 0.000 description 1
239000013067 intermediate product Substances 0.000 description 1
238000011835 investigation Methods 0.000 description 1
210000005053 lamin Anatomy 0.000 description 1
239000007942 layered tablet Substances 0.000 description 1
BVVCBYHYIPYXFG-UHFFFAOYSA-M lithium;oxolane;hydroxide Chemical compound [Li+].[OH-].C1CCOC1 BVVCBYHYIPYXFG-UHFFFAOYSA-M 0.000 description 1
235000010420 locust bean gum Nutrition 0.000 description 1
239000000711 locust bean gum Substances 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
229940098895 maleic acid Drugs 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
229940099690 malic acid Drugs 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
230000008018 melting Effects 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical compound COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 description 1
235000013336 milk Nutrition 0.000 description 1
239000008267 milk Substances 0.000 description 1
210000004080 milk Anatomy 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
235000019426 modified starch Nutrition 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
238000002703 mutagenesis Methods 0.000 description 1
231100000350 mutagenesis Toxicity 0.000 description 1
QPNOPWWAMGQISP-UHFFFAOYSA-N n,n'-dicyclohexylmethanediimine;methylsulfinylmethane Chemical compound CS(C)=O.C1CCCCC1N=C=NC1CCCCC1 QPNOPWWAMGQISP-UHFFFAOYSA-N 0.000 description 1
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
229920001206 natural gum Polymers 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
239000002773 nucleotide Substances 0.000 description 1
125000003729 nucleotide group Chemical group 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
229940041672 oral gel Drugs 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
239000002245 particle Substances 0.000 description 1
238000010647 peptide synthesis reaction Methods 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
JLTSGRABZPTRMS-UHFFFAOYSA-N phenyl(1,3-thiazol-2-yl)methanone Chemical compound C=1C=CC=CC=1C(=O)C1=NC=CS1 JLTSGRABZPTRMS-UHFFFAOYSA-N 0.000 description 1
229940012957 plasmin Drugs 0.000 description 1
229920002451 polyvinyl alcohol Polymers 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
229940114930 potassium stearate Drugs 0.000 description 1
ANBFRLKBEIFNQU-UHFFFAOYSA-M potassium;octadecanoate Chemical compound [K+].CCCCCCCCCCCCCCCCCC([O-])=O ANBFRLKBEIFNQU-UHFFFAOYSA-M 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
238000012746 preparative thin layer chromatography Methods 0.000 description 1
238000003825 pressing Methods 0.000 description 1
238000004393 prognosis Methods 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
ZJLMKPKYJBQJNH-UHFFFAOYSA-N propane-1,3-dithiol Chemical compound SCCCS ZJLMKPKYJBQJNH-UHFFFAOYSA-N 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
230000017854 proteolysis Effects 0.000 description 1
230000006337 proteolytic cleavage Effects 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
230000004044 response Effects 0.000 description 1
238000004007 reversed phase HPLC Methods 0.000 description 1
108091092562 ribozyme Proteins 0.000 description 1
229940100486 rice starch Drugs 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
235000012239 silicon dioxide Nutrition 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
235000009518 sodium iodide Nutrition 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
235000019345 sodium thiosulphate Nutrition 0.000 description 1
AKVBSROGSVKTID-UHFFFAOYSA-M sodium;ethyl acetate;chloride Chemical compound [Na+].[Cl-].CCOC(C)=O AKVBSROGSVKTID-UHFFFAOYSA-M 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
239000007892 solid unit dosage form Substances 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
235000010356 sorbitol Nutrition 0.000 description 1
238000007447 staining method Methods 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000012536 storage buffer Substances 0.000 description 1
150000004763 sulfides Chemical class 0.000 description 1
229940124530 sulfonamide Drugs 0.000 description 1
150000003457 sulfones Chemical class 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000013589 supplement Substances 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
150000005622 tetraalkylammonium hydroxides Chemical class 0.000 description 1
229960004072 thrombin Drugs 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
239000012588 trypsin Substances 0.000 description 1
229960001322 trypsin Drugs 0.000 description 1
238000011144 upstream manufacturing Methods 0.000 description 1
229960005356 urokinase Drugs 0.000 description 1
229960005486 vaccine Drugs 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
230000029812 viral genome replication Effects 0.000 description 1
238000005550 wet granulation Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0202—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/81—Protease inhibitors
- C07K14/8107—Endopeptidase (E.C. 3.4.21-99) inhibitors
- C07K14/811—Serine protease (E.C. 3.4.21) inhibitors
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Genetics & Genomics (AREA)
Biophysics (AREA)
Biochemistry (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
Virology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Crystallography & Structural Chemistry (AREA)
Gastroenterology & Hepatology (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Peptides Or Proteins (AREA)

HU0303436A 2000-12-12 2001-12-10 Diaril-peptidek mint a hepatitis C vírus NS3-szerin proteáz inhibitorai, ezeket tartalmazó gyógyszerkészítmények és alkalmazásuk HUP0303436A2 (hu)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US25486900P	2000-12-12	2000-12-12
PCT/US2001/047383 WO2002048172A2 (en)	2000-12-12	2001-12-10	Diaryl peptides as ns3-serine protease inhibitors of hepatits c virus

Publications (1)

Publication Number	Publication Date
HUP0303436A2 true HUP0303436A2 (hu)	2004-01-28

Family

ID=22965900

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HU0303436A HUP0303436A2 (hu)	2000-12-12	2001-12-10	Diaril-peptidek mint a hepatitis C vírus NS3-szerin proteáz inhibitorai, ezeket tartalmazó gyógyszerkészítmények és alkalmazásuk

Country Status (18)

Country	Link
US (1)	US6911428B2 (de)
EP (1)	EP1343807B1 (de)
JP (1)	JP4368581B2 (de)
KR (1)	KR20030091946A (de)
CN (1)	CN1301994C (de)
AR (1)	AR031905A1 (de)
AT (1)	ATE430166T1 (de)
AU (2)	AU3659102A (de)
CA (1)	CA2430458A1 (de)
DE (1)	DE60138567D1 (de)
ES (1)	ES2324594T3 (de)
HK (1)	HK1054394B (de)
HU (1)	HUP0303436A2 (de)
IL (1)	IL155842A0 (de)
MX (1)	MXPA03005219A (de)
PE (1)	PE20020691A1 (de)
WO (1)	WO2002048172A2 (de)
ZA (1)	ZA200304382B (de)

Families Citing this family (169)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CZ298749B6 (cs)	1996-10-18	2008-01-16	Vertex Pharmaceuticals Incorporated	Inhibitory serinových proteáz a farmaceutické prostředky s jejich obsahem
SV2003000617A (es)	2000-08-31	2003-01-13	Lilly Co Eli	Inhibidores de la proteasa peptidomimetica ref. x-14912m
PT1523489E (pt)	2002-06-28	2014-06-24	Centre Nat Rech Scient	Profármacos de nucleósido modificado em 2' e 3' para tratamento de infecções por flaviridae
EP1408031A1 (de) *	2002-10-09	2004-04-14	3 D Gene Pharma	Pyrolidinderivate zur Behandlung von Hepatitis C Virusinfektion
BRPI0419345B8 (pt)	2003-05-30	2021-05-25	Gilead Pharmasset Llc	uso do (2r)-2-desoxi-2-flúor-2-c-metil nucleosídeo e de uma composição farmacêutica que o compreende
DK1658302T3 (da)	2003-07-25	2010-11-22	Idenix Pharmaceuticals Inc	Purinnukleosidanaloge til behandling af sygdomme forårsaget af Flavirividae, herunder hepatitis C
WO2005021584A2 (en)	2003-08-26	2005-03-10	Schering Corporation	Novel peptidomimetic ns3-serine protease inhibitors of hepatitis c virus
PE20050374A1 (es)	2003-09-05	2005-05-30	Vertex Pharma	Inhibidores de proteasas de serina, en particular proteasa ns3-ns4a del vhc
KR20060085248A (ko) *	2003-09-26	2006-07-26	쉐링 코포레이션	Ｃ형 간염 바이러스 ｎｓ3 세린 프로테아제의마크로사이클릭 억제제
JP2007532479A (ja)	2003-11-20	2007-11-15	シェーリング　コーポレイション	Ｃ型肝炎ウイルスｎｓ３プロテアーゼの脱ペプチド化インヒビター
CA2549167A1 (en) *	2003-12-11	2005-06-30	Schering Corporation	Inhibitors of hepatitis c virus ns3/ns4a serine protease
GB0500020D0 (en)	2005-01-04	2005-02-09	Novartis Ag	Organic compounds
KR20120090077A (ko) *	2004-01-30	2012-08-16	얀센 알 앤드 디 아일랜드	Ｈｃｖｎｓ?３ 세린 프로테아제 저해제
US20050182252A1 (en)	2004-02-13	2005-08-18	Reddy K. R.	Novel 2'-C-methyl nucleoside derivatives
ES2328589T3 (es)	2004-02-27	2009-11-16	Schering Corporation	Compuestos de la prolina 3,4(ciclopentil) fusionados como inhibidores de la proteasa serina ns3 del virus de la hepatitis c.
DE602005023224D1 (de)	2004-02-27	2010-10-07	Schering Corp	Neuartige Verbindungen als Hemmer von Hepatitis C-Virus NS3-Serinprotease
MY145081A (en) *	2004-02-27	2011-12-15	Schering Corp	Sulfur compounds as inhibitors of hepatitis c virus ns3 serine protease
US7205330B2 (en)	2004-02-27	2007-04-17	Schering Corporation	Inhibitors of hepatitis C virus NS3 protease
US7192957B2 (en) *	2004-02-27	2007-03-20	Schering Corporation	Compounds as inhibitors of hepatitis C virus NS3 serine protease
US7816326B2 (en) *	2004-02-27	2010-10-19	Schering Corporation	Sulfur compounds as inhibitors of hepatitis C virus NS3 serine protease
CN1984922A (zh)	2004-05-20	2007-06-20	先灵公司	用作丙型肝炎病毒ns3丝氨酸蛋白酶抑制剂的取代脯氨酸
US7534767B2 (en)	2004-06-15	2009-05-19	Merck & Co., Inc.	C-purine nucleoside analogs as inhibitors of RNA-dependent RNA viral polymerase
CA2571079A1 (en)	2004-06-24	2006-02-02	Merck & Co., Inc.	Nucleoside aryl phosphoramidates for the treatment of rna-dependent rna viral infection
CN101023094B (zh)	2004-07-21	2011-05-18	法莫赛特股份有限公司	烷基取代的2-脱氧-2-氟代-d-呋喃核糖基嘧啶和嘌呤及其衍生物的制备
CA2577812A1 (en)	2004-08-27	2006-03-09	Schering Corporation	Acylsulfonamide compounds as inhibitors of hepatitis c virus ns3 serine protease
MX2007003085A (es)	2004-09-14	2007-08-02	Pharmasset Inc	Preparacion de 2'-fluoro-2'-alquilo sustituido u otras ribofuranosil pirimidinas y purinas opcionalmente sustituidas y sus derivados.
WO2006119061A2 (en)	2005-05-02	2006-11-09	Merck & Co., Inc.	Hcv ns3 protease inhibitors
CN101212970B (zh) *	2005-06-02	2010-07-21	先灵公司	Hcv蛋白酶抑制剂与表面活性剂的组合物
US20070237818A1 (en) *	2005-06-02	2007-10-11	Malcolm Bruce A	Controlled-release formulation of HCV protease inhibitor and methods using the same
WO2006130686A2 (en)	2005-06-02	2006-12-07	Schering Corporation	Hcv protease inhibitors in combination with food
AR054778A1 (es)	2005-06-17	2007-07-18	Novartis Ag	Uso de sangliferina en hcv
US20110104109A1 (en) *	2005-07-13	2011-05-05	Frank Bennett	Tetracyclic indole derivatives and their use for treating or preventing viral infections
TWI387603B (zh)	2005-07-20	2013-03-01	Merck Sharp & Dohme	Ｈｃｖｎｓ３蛋白酶抑制劑
KR20080036598A (ko)	2005-08-01	2008-04-28	머크 앤드 캄파니 인코포레이티드	Ｈｃｖｎｓ３ 프로테아제 억제제로서의 마크로사이클릭펩티드
US7632821B2 (en)	2005-08-09	2009-12-15	Merck & Co., Inc.	Ribonucleoside cyclic acetal derivatives for the treatment of RNA-dependent RNA viral infection
US7964624B1 (en)	2005-08-26	2011-06-21	Vertex Pharmaceuticals Incorporated	Inhibitors of serine proteases
AR055395A1 (es) *	2005-08-26	2007-08-22	Vertex Pharma	Compuestos inhibidores de la actividad de la serina proteasa ns3-ns4a del virus de la hepatitis c
US7705138B2 (en)	2005-11-11	2010-04-27	Vertex Pharmaceuticals Incorporated	Hepatitis C virus variants
AU2006315438A1 (en)	2005-11-11	2007-05-24	Vertex Pharmaceuticals Incorporated	Hepatitis C virus variants
US7816348B2 (en)	2006-02-03	2010-10-19	Boehringer Ingelheim International Gmbh	Viral polymerase inhibitors
CA2643688A1 (en)	2006-02-27	2007-08-30	Vertex Pharmaceuticals Incorporated	Co-crystals and pharmaceutical compositions comprising the same
WO2007109080A2 (en)	2006-03-16	2007-09-27	Vertex Pharmaceuticals Incorporated	Deuterated hepatitis c protease inhibitors
JP2009530382A (ja) *	2006-03-23	2009-08-27	シェーリングコーポレイション	Ｈｃｖプロテアーゼインヒビターとｃｙｐ３ａ４インヒビターとの組み合わせ、および関連する処置方法
CA2643680A1 (en)	2006-04-11	2007-11-22	Novartis Ag	Hcv/hiv inhibitors and their uses
GB0609492D0 (en)	2006-05-15	2006-06-21	Angeletti P Ist Richerche Bio	Therapeutic agents
MX341849B (es) *	2006-06-01	2016-09-05	Sanofi Aventis	Nitrilos espirociclicos como inhibidores de proteasa.
GB0612423D0 (en)	2006-06-23	2006-08-02	Angeletti P Ist Richerche Bio	Therapeutic agents
JP2010500978A (ja)	2006-08-17	2010-01-14	ベーリンガーインゲルハイムインターナショナルゲゼルシャフトミットベシュレンクテルハフツング	ウイルスポリメラーゼインヒビター
AU2007309546A1 (en)	2006-10-24	2008-05-02	Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A.	HCV NS3 protease inhibitors
AU2007309488B2 (en)	2006-10-24	2012-10-11	Merck Sharp & Dohme Corp.	HCV NS3 protease inhibitors
EP2079479B1 (de)	2006-10-24	2014-11-26	Merck Sharp & Dohme Corp.	Inhibitoren der hcv-ns3-protease
CN101568346B (zh)	2006-10-27	2015-11-25	默沙东公司	Hcv ns3蛋白酶抑制剂
CA2667031C (en)	2006-10-27	2013-01-22	Merck & Co., Inc.	Hcv ns3 protease inhibitors
GB0625349D0 (en)	2006-12-20	2007-01-31	Angeletti P Ist Richerche Bio	Therapeutic compounds
CA2672250C (en)	2006-12-20	2013-04-30	Ian Stansfield	Antiviral indoles
GB0625345D0 (en)	2006-12-20	2007-01-31	Angeletti P Ist Richerche Bio	Therapeutic compounds
JP5211068B2 (ja) *	2006-12-22	2013-06-12	メルク・シャープ・アンド・ドーム・コーポレーション	Ｈｃｖおよび関連するウイルス疾患の治療または予防のための４，５−環インドール誘導体
CA2674831A1 (en)	2006-12-22	2008-11-13	Schering Corporation	5,6-ring annulated indole derivatives and methods of use thereof
MX2009006880A (es)	2006-12-22	2009-07-03	Schering Corp	Derivados indolicos con anillo unido en las posiciones 4,5 para tratar o prevenir infecciones virales por virus de la hepatitis c e infecciones virales relacionadas.
WO2008106058A2 (en)	2007-02-27	2008-09-04	Vertex Pharmaceuticals Incorporated	Inhibitors of serine proteases
GEP20125645B (en) *	2007-02-27	2012-09-25	Vertex Pharma	Co-crystals and pharmaceutical compositions comprising the same
WO2008106167A1 (en) *	2007-02-28	2008-09-04	Conatus Pharmaceuticals, Inc.	Combination therapy comprising matrix metalloproteinase inhibitors and caspase inhibitors for the treatment of liver diseases
BRPI0808089A2 (pt) *	2007-02-28	2014-07-15	Conatus Pharmaceuticals Inc	Método para tratar uma doença do fígado, para diminuir um nível elevado de uma enzima do fígado, para inibir uma cascata de sinalização de tnf-alfa e uma cascata de sinalização de alfa-faz, para reduzir um dano ao fígado, para suprimir a apoptose excessiva em uma célula de fígado, e para inibir a replicação do vírus da hepatite c.
US7964580B2 (en)	2007-03-30	2011-06-21	Pharmasset, Inc.	Nucleoside phosphoramidate prodrugs
JP2010533699A (ja)	2007-07-17	2010-10-28	イステイチユート・デイ・リチエルケ・デイ・ビオロジア・モレコラーレ・ピ・アンジエレツテイ・エツセ・ピー・アー	Ｃ型肝炎感染症の治療のための大環状インドール誘導体
AU2008277377B2 (en)	2007-07-19	2013-08-01	Msd Italia S.R.L.	Macrocyclic compounds as antiviral agents
EP2188274A4 (de)	2007-08-03	2011-05-25	Boehringer Ingelheim Int	Virale polymerasehemmer
EP2197842B1 (de) *	2007-08-29	2012-05-23	Schering Corporation	2,3-substituierte indolderivate zur behandlung von virusinfektionen
CA2697500A1 (en)	2007-08-29	2009-03-12	Schering Corporation	2,3-substituted azaindole derivatives for treating viral infections
ES2447543T3 (es) *	2007-08-29	2014-03-12	Merck Sharp & Dohme Corp.	Derivados de indol sustituidos y métodos de utilización de los mismos
WO2009032198A1 (en)	2007-08-30	2009-03-12	Vertex Pharmaceuticals Incorporated	Co-crystals and pharmaceutical compositions comprising the same
US8383583B2 (en)	2007-10-26	2013-02-26	Enanta Pharmaceuticals, Inc.	Macrocyclic, pyridazinone-containing hepatitis C serine protease inhibitors
MX2010005261A (es)	2007-11-14	2010-10-15	Enanta Pharm Inc	Inhibidores macrocíclicos de proteasa de serina de hepatitis c de tetrazolilo.
CA2705586A1 (en) *	2007-11-16	2009-05-22	Schering Corporation	3-heterocyclic substituted indole derivatives and methods of use thereof
EP2222672B1 (de) *	2007-11-16	2013-12-18	Merck Sharp & Dohme Corp.	3-aminosulfonylsubstituierte indolderivate und verfahren zu deren anwendung
WO2009079353A1 (en)	2007-12-14	2009-06-25	Enanta Pharmaceuticals, Inc.	Triazole-containing macrocyclic hcv serine protease inhibitors
WO2009076747A1 (en)	2007-12-19	2009-06-25	Boehringer Ingelheim International Gmbh	Viral polymerase inhibitors
KR20100118991A (ko)	2008-02-04	2010-11-08	아이데닉스 파마슈티칼스, 인코포레이티드	매크로시클릭 세린 프로테아제 억제제
CA2719008A1 (en)	2008-03-20	2009-09-24	Enanta Pharmaceuticals, Inc.	Fluorinated macrocyclic compounds as hepatitis c virus inhibitors
TW200946541A (en)	2008-03-27	2009-11-16	Idenix Pharmaceuticals Inc	Solid forms of an anti-HIV phosphoindole compound
EP2271345B1 (de)	2008-04-28	2015-05-20	Merck Sharp & Dohme Corp.	Hcv-ns3 -proteasehemmer
WO2009152200A1 (en) *	2008-06-13	2009-12-17	Schering Corporation	Tricyclic indole derivatives and methods of use thereof
WO2010014134A1 (en)	2008-07-02	2010-02-04	Idenix Pharamaceuticals, Inc.	Compounds and pharmaceutical compositions for the treatment of viral infections
ME02024B (me)	2008-07-22	2015-05-20	Merck Sharp & Dohme	Makrociklična jedinjenja hinoksalina kao inhibitori hcv ns3 proteaze
TW201020245A (en)	2008-08-20	2010-06-01	Schering Corp	Ethynyl-substituted pyridine and pyrimidine derivatives and their use in treating viral infections
CA2734486A1 (en)	2008-08-20	2010-02-25	Southern Research Institute	Substituted pyridine and pyrimidine derivatives and their use in treating viral infections
ES2439009T3 (es)	2008-08-20	2014-01-21	Merck Sharp & Dohme Corp.	Derivados de piridina y pirimidina sustituidos con etenilo y su uso en el tratamiento de infecciones virales
WO2010022126A1 (en)	2008-08-20	2010-02-25	Schering Corporation	Azo-substituted pyridine and pyrimidine derivatives and their use in treating viral infections
US8044087B2 (en) *	2008-09-29	2011-10-25	Bristol-Myers Squibb Company	Hepatitis C virus inhibitors
JP6104504B2 (ja)	2008-12-23	2017-03-29	ギリアドファーマセットエルエルシー	ヌクレオシド類似体
TW201026715A (en)	2008-12-23	2010-07-16	Pharmasset Inc	Nucleoside phosphoramidates
CL2009002206A1 (es)	2008-12-23	2011-08-26	Gilead Pharmasset Llc	Compuestos derivados de pirrolo -(2-3-d]-pirimidin-7(6h)-tetrahidrofuran-2-il fosfonamidato, composicion farmaceutica; y su uso en el tratamiento de enfermedades virales.
WO2010080874A1 (en)	2009-01-07	2010-07-15	Scynexis, Inc.	Cyclosporine derivative for use in the treatment of hcv and hiv infection
WO2010082050A1 (en)	2009-01-16	2010-07-22	Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A.	Macrocyclic and 7-aminoalkyl-substituted benzoxazocines for treatment of hepatitis c infections
GB0900914D0 (en)	2009-01-20	2009-03-04	Angeletti P Ist Richerche Bio	Antiviral agents
US8102720B2 (en) *	2009-02-02	2012-01-24	Qualcomm Incorporated	System and method of pulse generation
JP5690286B2 (ja)	2009-03-04	2015-03-25	イデニクプハルマセウティカルス，インコーポレイテッド	ホスホチオフェン及びホスホチアゾールｈｃｖポリメラーゼ阻害剤
US8377962B2 (en)	2009-04-08	2013-02-19	Idenix Pharmaceuticals, Inc.	Macrocyclic serine protease inhibitors
US20110182850A1 (en)	2009-04-10	2011-07-28	Trixi Brandl	Organic compounds and their uses
US8512690B2 (en)	2009-04-10	2013-08-20	Novartis Ag	Derivatised proline containing peptide compounds as protease inhibitors
US8618076B2 (en)	2009-05-20	2013-12-31	Gilead Pharmasset Llc	Nucleoside phosphoramidates
TWI583692B (zh)	2009-05-20	2017-05-21	基利法瑪席特有限責任公司	核苷磷醯胺
CA2763140A1 (en)	2009-05-29	2010-12-02	Schering Corporation	Antiviral compounds composed of three linked aryl moieties to treat diseases such as hepatitis c
CN101605432B (zh) *	2009-07-10	2011-08-24	番禺南沙殷田化工有限公司	刚性印刷电路板的自动湿法贴膜方法
WO2011014487A1 (en)	2009-07-30	2011-02-03	Merck Sharp & Dohme Corp.	Hepatitis c virus ns3 protease inhibitors
US9284307B2 (en)	2009-08-05	2016-03-15	Idenix Pharmaceuticals Llc	Macrocyclic serine protease inhibitors
US20110117055A1 (en)	2009-11-19	2011-05-19	Macdonald James E	Methods of Treating Hepatitis C Virus with Oxoacetamide Compounds
AU2010324871A1 (en)	2009-11-25	2012-06-14	Merck Sharp & Dohme Corp.	Fused tricyclic compounds and derivatives thereof useful for the treatment of viral diseases
SG181797A1 (en)	2009-12-18	2012-07-30	Idenix Pharmaceuticals Inc	5,5-fused arylene or heteroarylene hepatitis c virus inhibitors
CA2785488A1 (en)	2009-12-22	2011-07-21	Merck Sharp & Dohme Corp.	Fused tricyclic compounds and methods of use thereof for the treatment of viral diseases
US9433621B2 (en)	2010-02-18	2016-09-06	Merck Sharp & Dohme Corp.	Substituted pyridine and pyrimidine derivatives and their use in treating viral infections
EP2545060B1 (de)	2010-03-09	2015-11-25	Merck Sharp & Dohme Corp.	Kondensierte tricyclische silylverbindngen und verfahren zu deren verwendung zur behandlung von viralen krankheiten
CL2011000716A1 (es)	2010-03-31	2012-04-20	Gilead Pharmasset Llc	Formas cristalinas 1 6 de (s)-isopropil-2-(((s)-(((2r.3r.4r.5r)-5-(2,4-dioxo-3,4-dihidropirimidin-1(2h)-il)-4-fluoro-3-hidroxi-4-metil tetrahidrofuran-2-il)metoxi)(fenoxi)fosforil)amino)propanoato; composicion y combinacion farmaceutica; y su uso para tratar una infeccion por el virus de la hepatitis c.
TWI515000B (zh)	2010-04-01	2016-01-01	伊迪尼克製藥公司	用於治療病毒感染之化合物及醫藥組合物
WO2012018534A2 (en)	2010-07-26	2012-02-09	Schering Corporation	Substituted biphenylene compounds and methods of use thereof for the treatment of viral diseases
EP2621279B1 (de)	2010-09-29	2018-04-04	Merck Sharp & Dohme Corp.	Kondensierte tetrazyklische derivate und verfahren zu ihrer verwendung zur behandlung von virenerkrankungen
EP2624826B1 (de)	2010-10-08	2018-07-18	Novartis AG	Zusammensetzungen enthaltend vitamin e und sulfamide mit ns3 hemmender wirkung
WO2012075140A1 (en)	2010-11-30	2012-06-07	Pharmasset, Inc.	Compounds
US9353100B2 (en)	2011-02-10	2016-05-31	Idenix Pharmaceuticals Llc	Macrocyclic serine protease inhibitors, pharmaceutical compositions thereof, and their use for treating HCV infections
US20120252721A1 (en)	2011-03-31	2012-10-04	Idenix Pharmaceuticals, Inc.	Methods for treating drug-resistant hepatitis c virus infection with a 5,5-fused arylene or heteroarylene hepatitis c virus inhibitor
CN103842369A (zh)	2011-03-31	2014-06-04	埃迪尼克斯医药公司	用于治疗病毒感染的化合物和药物组合物
EP2696681B1 (de)	2011-04-13	2018-10-03	Merck Sharp & Dohme Corp.	2'-substituierte nukleosidderivate und verfahren zu ihrer verwendung zur behandlung von virenerkrankungen
US9156872B2 (en)	2011-04-13	2015-10-13	Merck Sharp & Dohme Corp.	2′-azido substituted nucleoside derivatives and methods of use thereof for the treatment of viral diseases
WO2013033900A1 (en)	2011-09-08	2013-03-14	Merck Sharp & Dohme Corp.	Tetracyclic heterocycle compounds and methods of use thereof for the treatment of viral diseases
WO2013033899A1 (en)	2011-09-08	2013-03-14	Merck Sharp & Dohme Corp.	Substituted benzofuran compounds and methods of use thereof for the treatment of viral diseases
WO2013033901A1 (en)	2011-09-08	2013-03-14	Merck Sharp & Dohme Corp.	Heterocyclic-substituted benzofuran derivatives and methods of use thereof for the treatment of viral diseases
WO2013039855A1 (en)	2011-09-12	2013-03-21	Idenix Pharmaceuticals, Inc.	Compounds and pharmaceutical compositions for the treatment of viral infections
AR088441A1 (es)	2011-09-12	2014-06-11	Idenix Pharmaceuticals Inc	Compuestos de carboniloximetilfosforamidato sustituido y composiciones farmaceuticas para el tratamiento de infecciones virales
WO2013039876A1 (en)	2011-09-14	2013-03-21	Merck Sharp & Dohme Corp.	Silyl-containing heterocyclic compounds and methods of use thereof for the treatment of viral diseases
TW201331221A (zh)	2011-10-14	2013-08-01	Idenix Pharmaceuticals Inc	嘌呤核苷酸化合物類之經取代的３’，５’－環磷酸酯及用於治療病毒感染之醫藥組成物
WO2013074386A2 (en)	2011-11-15	2013-05-23	Merck Sharp & Dohme Corp.	Hcv ns3 protease inhibitors
US8889159B2 (en)	2011-11-29	2014-11-18	Gilead Pharmasset Llc	Compositions and methods for treating hepatitis C virus
CA3131037A1 (en)	2011-11-30	2013-06-06	Emory University	Antiviral jak inhibitors useful in treating or preventing retroviral and other viral infections
US20140356325A1 (en)	2012-01-12	2014-12-04	Ligand Pharmaceuticals Incorporated	Novel 2'-c-methyl nucleoside derivative compounds
WO2013133927A1 (en)	2012-02-13	2013-09-12	Idenix Pharmaceuticals, Inc.	Pharmaceutical compositions of 2'-c-methyl-guanosine, 5'-[2-[(3-hydroxy-2,2-dimethyl-1-oxopropyl)thio]ethyl n-(phenylmethyl)phosphoramidate]
EP2852604B1 (de)	2012-05-22	2017-04-12	Idenix Pharmaceuticals LLC	3',5'-cyclische phosphoramidat-prodrugs für hcv-infektion
US9296778B2 (en)	2012-05-22	2016-03-29	Idenix Pharmaceuticals, Inc.	3′,5′-cyclic phosphate prodrugs for HCV infection
AP3913A (en)	2012-05-22	2016-11-26	Idenix Pharamaceuticals Inc	D-amino acid compounds for liver disease
UA119315C2 (uk)	2012-07-03	2019-06-10	Гіліад Фармассет Елелсі	Інгібітори вірусу гепатиту с
SG11201502750UA (en)	2012-10-08	2015-06-29	Idenix Pharmaceuticals Inc	2'-chloro nucleoside analogs for hcv infection
US20140112886A1 (en)	2012-10-19	2014-04-24	Idenix Pharmaceuticals, Inc.	Dinucleotide compounds for hcv infection
EP2909222B1 (de)	2012-10-22	2021-05-26	Idenix Pharmaceuticals LLC	2',4'-verbrückten nukleoside für hcv-infektion
US20140140952A1 (en)	2012-11-14	2014-05-22	Idenix Pharmaceuticals, Inc.	D-Alanine Ester of Sp-Nucleoside Analog
EP2920195A1 (de)	2012-11-14	2015-09-23	IDENIX Pharmaceuticals, Inc.	D-alaninester eines rp-nukleosidanalogons
EP2935304A1 (de)	2012-12-19	2015-10-28	IDENIX Pharmaceuticals, Inc.	4'-fluor-nukleoside zur behandlung von hcv
WO2014121418A1 (en)	2013-02-07	2014-08-14	Merck Sharp & Dohme Corp.	Tetracyclic heterocycle compounds and methods of use thereof for the treatment of hepatitis c
WO2014121417A1 (en)	2013-02-07	2014-08-14	Merck Sharp & Dohme Corp.	Tetracyclic heterocycle compounds and methods of use thereof for the treatment of hepatitis c
WO2014137930A1 (en)	2013-03-04	2014-09-12	Idenix Pharmaceuticals, Inc.	Thiophosphate nucleosides for the treatment of hcv
US9309275B2 (en)	2013-03-04	2016-04-12	Idenix Pharmaceuticals Llc	3′-deoxy nucleosides for the treatment of HCV
SG11201507223TA (en)	2013-03-15	2015-10-29	Gilead Sciences Inc	Macrocyclic and bicyclic inhibitors of hepatitis c virus
EP2981542B1 (de)	2013-04-01	2021-09-15	Idenix Pharmaceuticals LLC	2',4'-fluor-nukleoside zur behandlung von hcv
US10005779B2 (en)	2013-06-05	2018-06-26	Idenix Pharmaceuticals Llc	1′,4′-thio nucleosides for the treatment of HCV
WO2015017713A1 (en)	2013-08-01	2015-02-05	Idenix Pharmaceuticals, Inc.	D-amino acid phosphoramidate pronucleotides of halogeno pyrimidine compounds for liver disease
JP2016529293A (ja)	2013-08-27	2016-09-23	ギリアドファーマセットエルエルシー	２つの抗ウイルス化合物の組合せ製剤
WO2015042375A1 (en)	2013-09-20	2015-03-26	Idenix Pharmaceuticals, Inc.	Hepatitis c virus inhibitors
WO2015061683A1 (en)	2013-10-25	2015-04-30	Idenix Pharmaceuticals, Inc.	D-amino acid phosphoramidate and d-alanine thiophosphoramidate pronucleotides of nucleoside compounds useful for the treatment of hcv
US10167298B2 (en)	2013-10-30	2019-01-01	Merck Sharp & Dohme Corp.	Pseudopolymorphs of an HCV NS5A inhibitor and uses thereof
WO2015066370A1 (en)	2013-11-01	2015-05-07	Idenix Pharmaceuticals, Inc.	D-alanine phosphoramidate pronucleotides of 2'-methyl 2'-fluoro guanosine nucleoside compounds for the treatment of hcv
EP3074399A1 (de)	2013-11-27	2016-10-05	Idenix Pharmaceuticals LLC	2'-dichlor- und 2'-fluor-2'-chlor-nukleosidanaloga für hcv-infektion
EP3083654A1 (de)	2013-12-18	2016-10-26	Idenix Pharmaceuticals LLC	4'-or-nukleoside zur behandlung von hcv
US10449210B2 (en)	2014-02-13	2019-10-22	Ligand Pharmaceuticals Inc.	Prodrug compounds and their uses
WO2015134780A1 (en)	2014-03-05	2015-09-11	Idenix Pharmaceuticals, Inc.	Solid prodrug forms of 2'-chloro-2'-methyl uridine for hcv
WO2015134561A1 (en)	2014-03-05	2015-09-11	Idenix Pharmaceuticals, Inc.	Pharmaceutical compositions comprising a 5,5-fused heteroarylene flaviviridae inhibitor and their use for treating or preventing flaviviridae infection
US20170066779A1 (en)	2014-03-05	2017-03-09	Idenix Pharmaceuticals Llc	Solid forms of a flaviviridae virus inhibitor compound and salts thereof
WO2015161137A1 (en)	2014-04-16	2015-10-22	Idenix Pharmaceuticals, Inc.	3'-substituted methyl or alkynyl nucleosides for the treatment of hcv
CN106687118A (zh)	2014-07-02	2017-05-17	配体药物公司	前药化合物及其用途
CN105153005A (zh) *	2015-08-05	2015-12-16	上海瑞博化学有限公司	一种4-羰基-脯氨酸衍生物的制备方法
JP2019533007A (ja) *	2016-09-13	2019-11-14	ハプロゲン・ゲーエムベーハー	抗ウイルス化合物
CN111788196A (zh)	2018-01-09	2020-10-16	配体药物公司	缩醛化合物及其治疗用途

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
BR8807310A (pt)	1987-11-18	1990-03-13	Chiron Corp	Polinucleotidio,polinucleotidio recombinante,vetor recombinante,celula hospedeira,sistema de expressao recombinante,celula transformada,polipeptidio,hcv,preparacao de polipeptidio,polipeptidio de hcv,polipeptidio purificado,polipeptidio recombinante,polipeptidio de fusao,anticorpo monoclonal,preparacao purificada de anticorpos policlonais,particula,sonda de polinucleotidio,kit anticorpo para epetopo de hcv,metodo para producao de polipeptidio,metodo para deteccao de acidos nucleicos de hcv,imunoensaio para detectar antigeno de hcv,imunoensaio para detectar anticorpos dirigidos contra antigeno de hcv,vacina para tratamento de infeccao de hcv,celula,celula infectada com hcv,metodo para producao de anticorpos para hcv e metodo para isolar cdna derivado do genoma de um agente infeccioso nao identificado
ATE132182T1 (de)	1989-02-01	1996-01-15	Asahi Glass Co Ltd	Azeotrope oder azeotropähnliche zusammensetzung auf der basis von chlorfluorkohlenwasserstoffen
DE69133617D1 (de)	1990-04-04	2009-07-23	Novartis Vaccines & Diagnostic	Protease von Hepatitis C Virus
WO1998007734A1 (en)	1996-08-21	1998-02-26	Hybridon, Inc.	Oligonucleotide prodrugs
CZ298749B6 (cs)	1996-10-18	2008-01-16	Vertex Pharmaceuticals Incorporated	Inhibitory serinových proteáz a farmaceutické prostředky s jejich obsahem
GB9623908D0 (en)	1996-11-18	1997-01-08	Hoffmann La Roche	Amino acid derivatives
US6323180B1 (en)	1998-08-10	2001-11-27	Boehringer Ingelheim (Canada) Ltd	Hepatitis C inhibitor tri-peptides
AR022061A1 (es)	1998-08-10	2002-09-04	Boehringer Ingelheim Ca Ltd	Peptidos inhibidores de la hepatitis c, una composicion farmaceutica que los contiene, el uso de los mismos para preparar una composicion farmaceutica, el uso de un producto intermedio para la preparacion de estos peptidos y un procedimiento para la preparacion de un peptido analogo de los mismos.
NZ521456A (en) *	2000-04-19	2004-07-30	Schering Corp	Macrocyclic NS3-Serine protease inhibitors of hepatitis C virus comprising alkyl and aryl alanine P2 moieties
MXPA03000627A (es) *	2000-07-21	2004-07-30	Schering Corp	Nuevos peptidos como inhibidores de proteasa serina-ns3 del virus de la hepatitis c.
WO2002008187A1 (en) *	2000-07-21	2002-01-31	Schering Corporation	Novel peptides as ns3-serine protease inhibitors of hepatitis c virus

2001
- 2001-12-10 HU HU0303436A patent/HUP0303436A2/hu unknown
- 2001-12-10 WO PCT/US2001/047383 patent/WO2002048172A2/en not_active Ceased
- 2001-12-10 AR ARP010105721A patent/AR031905A1/es unknown
- 2001-12-10 CN CNB018204759A patent/CN1301994C/zh not_active Expired - Fee Related
- 2001-12-10 AU AU3659102A patent/AU3659102A/xx active Pending
- 2001-12-10 US US10/013,071 patent/US6911428B2/en not_active Expired - Fee Related
- 2001-12-10 JP JP2002549703A patent/JP4368581B2/ja not_active Expired - Fee Related
- 2001-12-10 CA CA002430458A patent/CA2430458A1/en not_active Abandoned
- 2001-12-10 HK HK03106692.5A patent/HK1054394B/en not_active IP Right Cessation
- 2001-12-10 DE DE60138567T patent/DE60138567D1/de not_active Expired - Lifetime
- 2001-12-10 KR KR10-2003-7007731A patent/KR20030091946A/ko not_active Withdrawn
- 2001-12-10 EP EP01986126A patent/EP1343807B1/de not_active Expired - Lifetime
- 2001-12-10 AU AU2002236591A patent/AU2002236591B2/en not_active Expired - Fee Related
- 2001-12-10 ES ES01986126T patent/ES2324594T3/es not_active Expired - Lifetime
- 2001-12-10 IL IL15584201A patent/IL155842A0/xx unknown
- 2001-12-10 MX MXPA03005219A patent/MXPA03005219A/es active IP Right Grant
- 2001-12-10 AT AT01986126T patent/ATE430166T1/de not_active IP Right Cessation
- 2001-12-11 PE PE2001001236A patent/PE20020691A1/es not_active Application Discontinuation
2003
- 2003-06-04 ZA ZA200304382A patent/ZA200304382B/en unknown

Also Published As

Publication number	Publication date
HK1054394B (en)	2009-09-25
ATE430166T1 (de)	2009-05-15
KR20030091946A (ko)	2003-12-03
CN1301994C (zh)	2007-02-28
DE60138567D1 (de)	2009-06-10
WO2002048172A3 (en)	2003-06-19
AR031905A1 (es)	2003-10-08
IL155842A0 (en)	2003-12-23
JP4368581B2 (ja)	2009-11-18
EP1343807A2 (de)	2003-09-17
WO2002048172A2 (en)	2002-06-20
EP1343807B1 (de)	2009-04-29
ZA200304382B (en)	2004-09-13
CA2430458A1 (en)	2002-06-20
US6911428B2 (en)	2005-06-28
US20020147139A1 (en)	2002-10-10
CN1501942A (zh)	2004-06-02
PE20020691A1 (es)	2002-08-03
JP2004532812A (ja)	2004-10-28
AU2002236591B2 (en)	2005-07-14
HK1054394A1 (en)	2003-11-28
MXPA03005219A (es)	2003-09-25
ES2324594T3 (es)	2009-08-11
AU3659102A (en)	2002-06-24

Legal Events

Date	Code	Title	Description
2006-08-28	FD9A	Lapse of provisional protection due to non-payment of fees

Publication	Publication Date	Title
JP4368581B2 (ja)	2009-11-18	Ｃ型肝炎ウイルスのｎｓ３−セリンプロテアーゼ阻害剤としてのジアリールペプチド
EP1301486B1 (de)	2009-07-01	Imidazolidinone als ns3-serin protease inhibitoren von hepatitis c virus
JP4748911B2 (ja)	2011-08-17	Ｎ−環状ｐ２部分を含むｃ型肝炎ウイルスの大環状ｎｓ３‐セリンプロテアーゼ阻害剤
JP4748912B2 (ja)	2011-08-17	アルキルおよびアリールアラニンｐ２部分を含むｃ型肝炎ウイルスに対する大員環ｎｓ３−セリンプロテアーゼ阻害剤
US7592419B2 (en)	2009-09-22	Macrocyclic inhibitors of hepatitis C virus NS3-serine protease
JP4298289B2 (ja)	2009-07-15	Ｃ型肝炎ウイルスのｎｓ３−セリンプロテアーゼ阻害剤としての新規ペプチド
EP2134739B1 (de)	2010-12-01	Schwefelverbindungen als hemmer der ns3-serin-protease des hepatitis-c-virus
JP4452441B2 (ja)	2010-04-21	Ｃ型肝炎ウイルスのｎｓ３−セリンプロテアーゼ阻害剤としての新規ペプチド
JP2009057390A (ja)	2009-03-19	Ｃ型肝炎ウイルスのｎｓ３セリンプロテアーゼ阻害剤としての新規ペプチド
AU2002236591A1 (en)	2002-08-29	Diaryl peptides as NS3-serine protease inhibitors of hepatits C virus
KR20060118532A (ko)	2006-11-23	Ｃ형 간염 바이러스 ｎｓ３／ｎｓ４ａ 세린 프로테아제의억제제
JP2007525511A (ja)	2007-09-06	Ｃ型肝炎ウイルスｎｓ３セリンプロテアーゼの新規のインヒビターとしての化合物
AU2001280637A1 (en)	2002-05-02	Novel peptides as NS3-serine protease inhibitors of hepatitis C virus